Immune system markers of neuroinflammation in patients with clinical diagnose of neuromyelitis optica

Abstract

-Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system characterized by the association of a serious myelitis and unilateral or bilateral optic neuritis. The present study aimed to analyze the immunological parameters of NMO patients with diagnosis established based on Wingerchuck et al. (1999) criteria. Production of IgG and IgA antibodies to antigens of MBP, PLP 95-116, MOG 92-106, and the cytokines interleukin-4 (IL-4) and interferon-γ (INF-γ) were assessed by Elisa assay. The cohort was formed by 28 NMO patients and a matched healthy control group. NMO patients had significant high levels of IgG to MOG (p<0.0001), PLP (p=0.0002) and MBP (p<0.0001), and solely IgA to MBP (p<0.0001). INF-γ (p=0.61) levels were similar to healthy controls. Increased production of IL-4 (p=0.0084) indicates an important role for this cytokine in the activation of Th2 regulatory cells and of the IgA producers B lymphocyte indicating activation of humoral immunity.KEy WOrds: neuromyelitis optica, autoantigens, cytokines, myelin basic protein. marcadores imunológicos em pacientes com diagnóstico de neuromielite ópticaResumo -A neuromielite óptica (NMO) é doença inflamatória do sistema nervoso central, caracterizada por mielite aguda ou subaguda grave e neurite óptica unilateral ou bilateral. Este estudo objetiva analisar parâmetros imunológicos de pacientes com critérios de Wingerchuck et al. (1999) para NMO. O método de ELIsA avaliou a produção de IgG e IgA para antígenos da proteína básica da mielina (MBP), o proteolipídeo (PLP) 95-116, a glicoproteina associada ao oligodendrócito (MOG) 92-106 e as citocinas interleucina-4 (IL-4) e interferon-gama (INF-γ). Foram incluídos 28 pacientes com NMO pareados com controles saudáveis. Pacientes com NMO apresentaram níveis significativamente elevados de imunoglobulinas reativas dos isotipos IgG para MOG (p<0,0001), PLP (p=0,0002) e MBP (p<0,0001) e IgA somente para MBP (p<0,0001). Os níveis de INF-γ (p=0,61) foram semelhantes aos controles. A produção elevada de IL-4 (p=0,0084) indica papel importante na ativação de células regulatórias Th2 e linfócitos B produtores de IgA e da ativação da imunidade humoral.PALAVrAs-CHAVE: neuromielite óptica, autoantígenos, citocinas, proteína básica da mielina.

Neuromyelitis optica: phenotypic characteristics in a Brazilian case series

“…Neuromyelitis optica patients are predominantly female, with a ratio higher than that of multiple sclerosis; the average age at onset is older, usually by the end of the fourth decade of life; and the prevalence of non-white patients is higher than that of other demyelinating diseases 12,13,14,15,16,17,18 . These demographic characteristics were also present in the current Brazilian NMO case series and were similar to those reported for other case series in the country 19,20,21,22 . The exceptions include a younger age at onset in the Adoni et al 21 series, in which only patients with recurrent NMO were analyzed, and lower female-to-male ratios in the Alves-Leon et al 20 and Bichuetti et al 22 series (Table 4).…”

“…These demographic characteristics were also present in the current Brazilian NMO case series and were similar to those reported for other case series in the country 19,20,21,22 . The exceptions include a younger age at onset in the Adoni et al 21 series, in which only patients with recurrent NMO were analyzed, and lower female-to-male ratios in the Alves-Leon et al 20 and Bichuetti et al 22 series (Table 4). All NMO patients in our series exhibited extensive longitudinal spinal cord lesions in at least one spinal MRI, and none had imaging features suggestive of multiple sclerosis.…”

Association of anti-aquaporin-4 antibody-positive neuromyelitis optica with myasthenia gravis

“…Increased production of interleukin-4 in NMO patients indicates an important role of this cytokine in the activation of Th2 regulatory cells [18]. On the other hand, anti-AChR antibody-positive MG is mediated by autoantibodies against AChR in the postsynaptic membrane [4].…”

No Overlap among Serum GAD65, NMDAR and AQP4 Antibodies in Patients with Neuromyelitis Optica Spectrum Disorders

“…NMO lesions show a marked deposition of immunoglobulin and complement in a characteristic perivascular rosette pattern along the outer rim of thickened vessel walls [4]. NMO has been associated with many other autoimmune diseases and even more frequently with the presence of circulating autoantibodies in the absence of clinical manifestations of other diseases [5,6,7]. A specific IgG autoantibody selectively targeting aquaporin-4 (AQP4) has been established as a useful biomarker to distinguish NMO from multiple sclerosis (MS) [3,8,9].…”